To see how brain works, switch amygdala ‘off’

Temporarily turning off one part of the brain changes patterns of activity across other parts as well, according to a new study with monkeys.

The findings suggest that alterations in the functional connectivity of the brain in humans may have implications for disorders such as schizophrenia and autism.

For the study, published in the journal Neuron, scientists targeted the amygdala—a small, almond-shaped region deep within the brain known to be important for fear and other emotions.

Using a technology called “designer receptors exclusively activated by designer drugs,” (DREADDs), researchers genetically modified the neurons of the amygdala to produce molecular on-off switches, or receptors, that are triggered by a drug administered to the animal. When the drug is injected, the receptors shut down activity in the amygdala—effectively turning off this brain region.

The researchers then evaluated the activity in the rest of the brain using functional magnetic resonance imaging, or fMRI, when the amygdala was either on or turned off. FMRI allows researchers to measure what is called functional connectivity—the extent to which different brain regions coordinate their activity and form networks.

When the amygdala was turned off, patterns of brain activity in other brain regions either decreased or increased. Areas known to be well-connected to the amygdala were particularly affected, but so were brain regions that have no known connections.

“This type of study, where a brain region is turned on and off while carrying out functional imaging, has never been done previously in a monkey,” says David Amaral, professor of psychiatry and behavioral sciences at the University of California Davis, who is also director of research at the MIND Institute.

“This technology establishes a new era of behavioral neuroscience that reduces the number of animal subjects since each subject acts as its own control. We see very direct linkage between this research and our overarching interest in understanding the neural alterations associated with autism.”

The findings represent “groundbreaking research that has enormous clinical potential,” says John Morrison, director of the California National Primate Research Center. “Similar techniques in the future may control abnormal activity in disorders such as epilepsy and Parkinson’s disease. Understanding how brain areas form networks is critical for determining the origin of pathology and eventually developing effective interventions.”

Other researchers from UC Davis and from Oregon Health and Science University and the Rotman Research Institute, Baycrest Centre, Toronto are coauthors of the study, which was funded by the National Institutes of Health.